DESCRIPTION: (Applicant's Abstract) Improved methods to monitor treatment compliance and efficacy is an important goal of drug-abuse treatment programs and clinical trials for new treatment regimens. Monitoring drug use during pregnancy is also an important clinical goal. Compared to urine, plasma and blood, hair may provide a longer window to monitor for drugs and other compounds due to its slow growth and possible permanent retention of drugs. The presence of certain drugs and their metabolites has been demonstrated in human hair at times when plasma and urine drug concentrations are not measurable. The goal of this project is to acquire knowledge regarding the suitability of quantitative, segmental human hair analysis for determination of drug exposure in clinical settings. Specific marker substances will be used to establish reference points (with respect to time) in human hair. To achieve these objectives, the following specific aims are proposed: (1) To develop quantitative analytical methods for hair utilizing LC/MS/MS. Ultra-sensitive and specific procedures using liquid chromatography and tandem mass spectrometry will be developed for the combined detection and quantitation of a treatment drug (buprenorphine, 1-alpha-acetylmethadol, or methadone), drugs of abuse (morphine, heroin) and marker substances (phenazopyridine or ofloxacin) in hair. Also, specific and selective decontamination procedures will be developed to minimize the potential bias of environmental contamination of hair for drugs of interest and to maximize the reliability of measured quantitative drug concentrations. (2) To determine if quantitative analysis of hair can be used to evaluate recidivism and treatment compliance. Administration of a marker substance such as phenazopyridine or ofloxacin will be used to establish reference points in human hair between which drug use and treatment compliance or recidivism in clinical drug-abuse studies can be measured. We will also determine if quantitative measures of drug concentrations in hair are dependent upon the dose and route of drug administration. (3) To determine if quantitative analysis of hair can be used to evaluate fetal drug exposure in pregnant women receiving drug treatment. Specifically, we will determine if there is a relationship between maternal exposure to a treatment drug (methadone) during pregnancy and neonatal hair concentrations of methadone at birth. Preliminary data presented demonstrate that we are able to perform all aspects of this proposal and that we will clearly be able to progress from analytical methods development, to decontamination studies, to in vivo human and animal studies of marker substance incorporation into hair, and to studies of fetal drug exposure.